Increased cathepsin D level in the serum of patients with metastatic breast carcinoma detected with a specific pro-cathepsin D immunoassay

Brouillet, Jean‐Paul; Dufour, Franck; Lémamy, Guy Joseph; Garcia, Marcel; Schlup, Nicolas; Grenier, Jean; Mani, Jean‐Claude; Rochefort, Henri

doi:10.1002/(sici)1097-0142(19970601)79:11<2132::aid-cncr10>3.0.co;2-x

Cited by 52 publications

(37 citation statements)

References 13 publications

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“…The determination of CD and pCD in tissue and serum as an independent cancer prognostic marker has been suggested (Tandon et al, 1990;Brouillet et al, 1997). In the current study, we have confirmed secretion of pCD by HaCaT cells, cultured in serum-free media.…”

Section: Discussionmentioning

confidence: 99%

Procathepsin D secreted by HaCaT keratinocyte cells – A novel regulator of keratinocyte growth

Vashishta¹,

Ohri²,

Větvičková³

et al. 2007

European Journal of Cell Biology

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Procathepsin D (pCD), the precursor form of lysosomal aspartic protease, is overexpressed and secreted by various carcinomas. The fact that secreted pCD plays an essential role in progression of cancer has been established. In this study, we describe substantial secretion of pCD by the human keratinocyte cell line HaCaT, under serum-free conditions. Moreover, exogenous addition of purified pCD enhanced the proliferation of HaCaT cells. The proliferative effect of pCD was inhibited by a monoclonal antibody against the activation peptide (AP) of pCD. Treatment of HaCaT cells with pCD or AP led to the secretion of a set of cytokines that might promote the growth of cells in a paracrine manner. The role of secreted pCD and its mechanism of action were studied in a scratch wound model and the presence of pCD and AP enhanced regeneration, while this effect was reversed by the addition of anti-AP antibody. Expression and secretion of pCD was upregulated in HaCaT cells exposed to various stress conditions. Taken together, our results strongly suggest that the secretion of pCD is not only linked to cancer cells but also plays a role in normal physiological conditions like wound healing and tissue remodeling.

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Section: Discussionmentioning

confidence: 99%

Procathepsin D secreted by HaCaT keratinocyte cells – A novel regulator of keratinocyte growth

Vashishta¹,

Ohri²,

Větvičková³

et al. 2007

European Journal of Cell Biology

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“…Other studies have indicated a prognostic role for cath-D over-expression by reactive stromal cells [59][60][61][62]. Pro-cath-D is also increased in the plasma of patients with metastatic breast cancer [63,64], indicating that part of the pro-cath-D secreted by tumors can be released into the circulation. [65,66].…”

Section: Over-expression Of Cath-d In Breast Cancer Cellsmentioning

confidence: 99%

Cathepsin D: newly discovered functions of a long-standing aspartic protease in cancer and apoptosis

et al. 2006

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“…When antibodies specifically recognizing pCD have been used, two groups reported findings of elevated concentration of pCD in serum of metastatic breast cancer patients, 81,82 suggesting that, at least in final stages of cancer, pCD is released into the bloodstream. It is important that the activation peptide sequence is recognized by the immune system as a non-self-structure and triggers the production of specific antiactivation peptide antibodies.…”

Section: Cancer Gene Therapymentioning

confidence: 99%

Procathepsin D in breast cancer: What do we know? Effects of ribozymes and other inhibitors

2002

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Procathepsin D (pCD) is a major secreted glycoprotein in some human breast and other cancer cell lines. Several groups proposed that pCD served as a growth factor for these cell lines. Secreted pCD has been demonstrated in tissue section, tissue culture supernatants, carcinoma cytosols, and nipple aspirates. Moreover, several clinical studies suggested a potential role for this molecule in metastasis because its concentration in primary tumors correlated with an increased incidence of tumor metastases. In this paper, the effects of pCD were evaluated by proliferation in vitro and by mouse studies in vivo. Subsequent flow cytometry experiments showed the specificity of pCD binding to cancer cells. Cell cultivation showed that addition of either pCD or its activation peptide stimulates growth of cancer cells. These effects can be inhibited both in vitro and in vivo by anti-pCD antibodies. In addition, production of pCD can be inhibited by specifically designed ribozymes. This paper is focused on mitogenic effects of pCD, which seem to involve interaction of the activation peptide with as yet unidentified receptor. Different mechanisms by which pCD could promote development and spread of cancer cells are discussed.

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Increased cathepsin D level in the serum of patients with metastatic breast carcinoma detected with a specific pro-cathepsin D immunoassay

Abstract: An increased level of cath-D in the serum of breast carcinoma patients is a late event observed only in patients with metastatic disease. This increased circulating level is more likely due to increased secretion of the proenzyme rather than to tumor cell lysis.

Cited by 52 publications

References 13 publications

Procathepsin D secreted by HaCaT keratinocyte cells – A novel regulator of keratinocyte growth

Procathepsin D secreted by HaCaT keratinocyte cells – A novel regulator of keratinocyte growth

Cathepsin D: newly discovered functions of a long-standing aspartic protease in cancer and apoptosis

Procathepsin D in breast cancer: What do we know? Effects of ribozymes and other inhibitors

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